Coinfection with hepatitis B virus (HBV) is common among HIV-infected patients. HIV accelerates the progression of HBV-related liver fibrosis, and HIV/HBV patients have higher risks of end-stage liver disease (ESLD) and hepatocellular carcinoma (HCC) than those with HIV or HBV alone. As a result, these liver complications are major causes of morbidity and mortality in HIV/HBV patients. To reduce the risks of these events, anti-HBV-active antiretroviral therapy (ART), preferably with tenofovir, is recommended in all HIV/HBV patients with the goal of suppressing both viruses to undetectable levels. Despite the use of tenofovir-based ART, rates of liver complications remain high among HIV/HBV patients. Further, complete HBV suppression is not readily achieved in a large proportion of HIV/HBV patients in clinical practice, and detectable HBV, along with HIV viremia, may be important contributors to the high rates of ESLD and HCC observed in this group. Adequately powered cohort studies of HIV/HBV patients on tenofovir-based ART are therefore needed to determine the mechanisms for liver complications in these individuals. Studies of HIV/HBV patients have been limited by small sample sizes, short follow-up, inadequate collection of important variables, and have not evaluated clinical endpoints such as ESLD or HCC. This proposal will address these knowledge gaps and existing limitations by utilizing data from the North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD) to create the largest cohort of HIV/HBV patients and evaluate ESLD and HCC events that have been confirmed by medical record review. In this application, we will use the unique data of the NA-ACCORD to conduct a series of epidemiologic studies to evaluate the impact of detectable HBV DNA and HIV RNA on liver complications in HIV/HBV patients receiving tenofovir-based antiretroviral therapy. Aim 1 will determine the risk of liver complications, defined by ESLD and HCC events, associated with detectable HBV DNA among HIV/HBV patients on tenofovir-based antiretroviral therapy. Aim 2 will quantify the risk of liver complications with HIV viremia in thee individuals. Our analyses will also identify other important determinants of liver events (e.g., lo CD4 count, obesity, diabetes, hazardous alcohol use) in these patients. The completion of these aims will address critical knowledge gaps on the mechanisms of liver complications among HIV/HBV patients. If our hypotheses are confirmed and detectable HBV and HIV viremia are identified as important contributors to adverse hepatic outcomes, interventions would need to be developed and evaluated to increase rates of complete suppression of these viruses. These findings will motivate new research proposals on optimal HBV treatment strategies in HIV-infected patients that may change the clinical paradigm for HBV management in HIV.